Ceramide synthases (CerS) synthesize chain length specific ceramides (Cer), which mediate cellular processes in a chain length-dependent manner. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed that the genetic deletion of CerS2 suppresses EAE pathology by interaction with granulocyte-colony stimulating factor (G-CSF) signaling and CXC motif chemokine receptor 2 (CXCR2) expression, leading to impaired neutrophil migration. In the present study, we investigated the importance of Cers and their synthesizing/metabolizing enzymes in MS. For this purpose, a longitudinal study with 72 MS patients and 25 healthy volunteers was performed. Blood samples were collected from healthy controls and MS patients over 1- or 3-year periods, respectively. Immune cells were counted using flow cytometry, ceramide levels were determined using liquid chromatography-tandem mass spectrometry, and mRNA expression was analyzed using quantitative PCR. In white blood cells, C16-LacCer and C24-Cer were down-regulated in MS patients in comparison with healthy controls. In plasma, C16-Cer, C24:1-Cer, C16-GluCer, and C24:1-GluCer were up-regulated and C16-LacCer was down-regulated in MS patients in comparison with healthy controls. Blood samples from MS patients were characterized by an increased B-cell number. However, there was no correlation between B-cell number and Cer levels. mRNA expression of Cer metabolizing enzymes and G-CSF signaling enzymes was significantly increased in MS patients. Interestingly, G-CSF receptor (G-CSFR) and CXCR2 mRNA expression correlated with CerS2 and UDP-glucose Cer glucosyltransferase (UGCG) mRNA expression. In conclusion, our results indicate that Cer metabolism is linked to G-CSF signaling in MS.
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A scanning electron micrograph (digitally altered and colourized, 4000× magnification) depicting a mesenchymal stem cell (orange) encapsulated in a self-assembling peptide hydrogel. In volume 132, issue 17 of Clinical Science, McFetridge et al. discuss the use of hydrogel materials to unlock the potential of stem cell therapy to treat chronic kidney disease. This image was provided by the authors and produced in collaboration with Dr Simon Crawford at the Ramaciotti Centre for Cryo-Electron Microscopy, and the Monash Teaching Resource Support Unit.
Research Article|
September 14 2018
The relevance of ceramides and their synthesizing enzymes for multiple sclerosis
Jennifer Kurz;
Jennifer Kurz
1Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Branch for Translational Medicine and Pharmacology TMP, Theodor-Stern-Kai 7, 60596 Frankfurt/Main, Germany
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Robert Brunkhorst;
Robert Brunkhorst
2Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16, 60528 Frankfurt/Main, Germany
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Christian Foerch;
Christian Foerch
2Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16, 60528 Frankfurt/Main, Germany
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Leonard Blum;
Leonard Blum
3Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany
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Marina Henke;
Marina Henke
1Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Branch for Translational Medicine and Pharmacology TMP, Theodor-Stern-Kai 7, 60596 Frankfurt/Main, Germany
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Laureen Gabriel;
Laureen Gabriel
1Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Branch for Translational Medicine and Pharmacology TMP, Theodor-Stern-Kai 7, 60596 Frankfurt/Main, Germany
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Thomas Ulshöfer;
Thomas Ulshöfer
1Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Branch for Translational Medicine and Pharmacology TMP, Theodor-Stern-Kai 7, 60596 Frankfurt/Main, Germany
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Nerea Ferreirós;
Nerea Ferreirós
3Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany
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Michael J. Parnham;
Michael J. Parnham
1Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Branch for Translational Medicine and Pharmacology TMP, Theodor-Stern-Kai 7, 60596 Frankfurt/Main, Germany
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Gerd Geisslinger;
Gerd Geisslinger
3Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany
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Susanne Schiffmann
3Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany
Corespondence: Susanne Schiffmann ([email protected])
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Publisher: Portland Press Ltd
Received:
June 14 2018
Revision Received:
August 07 2018
Accepted:
August 12 2018
Accepted Manuscript online:
August 17 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (17): 1963–1976.
Article history
Received:
June 14 2018
Revision Received:
August 07 2018
Accepted:
August 12 2018
Accepted Manuscript online:
August 17 2018
Citation
Jennifer Kurz, Robert Brunkhorst, Christian Foerch, Leonard Blum, Marina Henke, Laureen Gabriel, Thomas Ulshöfer, Nerea Ferreirós, Michael J. Parnham, Gerd Geisslinger, Susanne Schiffmann; The relevance of ceramides and their synthesizing enzymes for multiple sclerosis. Clin Sci (Lond) 14 September 2018; 132 (17): 1963–1976. doi: https://doi.org/10.1042/CS20180506
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